Case Description
The patient is a previously healthy 2 year old Caucasian male referred for admission under the pediatric hospitalist service due to swelling of the face, abdomen, and the extremities. History showed initial symptoms of low-grade fever occurring intermittently for a week together with right eye swelling. Upon presentation to his primary care provider, it was treated as cellulitis with Amoxicillin-clavulanate however no improvement was noted. The patient on follow-up after 2 days tested positive for COVID-19 infection. Due to non-response and progression of swelling to both legs, the patient was started on oral prednisolone for possible allergy and referred to an allergy specialist. His symptoms persisted and on the day of referral was worsened by abdominal distention as noticed by the mother.
Upon admission, vital signs included heart rate of 112 beats per minute, respiratory rate of 24 breaths per minute, blood pressure of 110/78, and oxygen saturation of 96% on room air. Laboratory work up included CBC which showed a white count of 7,600 with hemoglobin of 12.4 g/dL, and hematocrit of 37.3%. Urinalysis on catheterization showed proteinuria >500 mg/dl, moderate blood, and 10-20 RBC/hpf. Metabolic panel showed serum sodium of 136 mmol/L, BUN of 10 mg/dL, creatinine of 0.17 mg/dL, hypoalbuminemia with serum albumin of 1.6 g/dL, and elevated urine protein 503 mg/dl and urine creatinine 69.1 mg/dl with a ratio of 7.27. Serum triglyceride and cholesterol were also both elevated at 599 mg/dL and 668 mg/dL, respectively. Complement levels were normal with C3 at 105 mg/dL and C4 of 28 mg/dL.
The clinical and laboratory findings were both consistent and met the criteria for the diagnosis of new onset nephrotic syndrome, which includes edema, nephrotic range proteinuria, hypoalbuminemia, and hyperlipidemia, and The patient was then started on oral prednisolone at 2 mg/kg/day, dietary sodium and fluid restriction, and diuretic therapy with furosemide. Upon consultation with the Pediatric Nephrology service, the patient was transferred to a tertiary children’s hospital due to concerns of possible development of complications such as thrombosis related to hypercoagulability and worsening infection from an immunocompromised state. Management at the tertiary facility included IV steroid, diuretics, and oral proton pump inhibitor.
The patient achieved remission with the anasarca significantly improved, resolution of proteinuria with negative urine protein and urine to protein to creatinine ratio of 1.2, and the patient’s weight back down to 14.5 kg. He continued to follow up with the Pediatric Nephrology service as an outpatient.
Discussion :
It is hypothesized that the pathology due to COVID-19 may be secondary to the SARS-CoV and SARS-CoV-2 ability to conjugate with angiotensin-converting enzyme 2 (ACE2) receptors in lung epithelium thereby replicating and downregulating these receptors. The resulting diminished ability to degrade angiotensin II (ATII) results in an upsurge of ATII leading to systemic inflammation. The effects include vasodilation, thrombosis, and further inflammation in multiple organs with ACE2 receptors including the kidneys14.
Renal features of adults with COVID-19 infection include nephropathy, thrombotic microangiopathy, acute kidney injury, and acute tubular necrosis2,15. Histopathologically, podocytopathy and collapsing glomerulopathy are two of the most common findings with African ancestry being a significant demographic factor16. Anandh and Bannur (2022) also described its possible immunomodulatory effects in a case series of 3 adult patients who developed nephrotic syndrome four to six weeks post COVID-19 infection with findings of two being steroid responsive while the third did not achieve full remission with steroids but responded well to tacrolimus17.
Currently there are no studies that provide a direct correlation between COVID-19 and new onset of NS. However, there are some reports on COVID-19 infection causing worsening renal function in patients with CKD. Melgosa (2020) described 16 children with CKD where COVID-19 infection caused worsening of GFR in three, and relapse in two children with steroid dependent nephrotic syndrome18. In a case series reported on 186 pediatric patients with Multisystem Inflammatory Syndrome in Children (MIS-C), 92% of the patients had four or more laboratory markers such as elevated erythrocyte sedimentation rate, lymphocytopenia, neutrophilia, hypoalbuminemia, elevated ferritin etc. Hypoalbuminemia was a laboratory finding in almost half of the cases19. Basiratnia et al. (2021) described two cases, a 16 and 17 year old, both males, with acute necrotizing glomerulonephritis in the context of COVID-19 infection. Both reported cases underwent hemodialysis; however, the case with more chronic features, which included interstitial fibrosis, arteriolar wall thickening, and fibrinoid necrosis on kidney biopsy progressed to kidney failure while the other responded well to glucocorticoid therapy20. In existing pediatric literature on MIS-C in the United States, renal involvement of any kind has been reported in 3-13% and 2-8% is manifested as Acute Kidney Injury (AKI)20. AKI remains the most encountered renal manifestation of COVID-19.
Among children, reports of nephrotic range proteinuria as a complication of COVID-19 are minimal. To our knowledge, this is only the fourth pediatric case reporting new onset NS during a COVID-19 infection. Similar to the three previously published case reports, our patient presented with concurrent positive PCR test for COVID-19 and symptoms of NS such as periorbital edema that progressed to include the abdomen and extremities. The patient showed significant response to steroid treatment with improvement of proteinuria and edema.
This report adds to the limited literature on pediatric nephrotic syndrome in association with a COVID-19 infection. It will help provide a better understanding on the course of the disease, response to steroid treatment, and the risk of developing complications, if any, such as end stage renal disease. The patient in this case showed a steroid responsive course similar to the three children previously reported.